Purinergic receptors are cell surface receptors that interact with extracellular adenine or uridine nucleotides and nucleosides. These receptors are present throughout the central nervous system and peripheral tissues and play a role in numerous physiological responses.
The purinergic receptors are broadly divided into two major receptor types, P.sub.1 and P.sub.2, which are defined by their level of interaction with the adenine nucleotides and nucleosides. Where P.sub.1 receptors are activated by adenosine and exhibit a potency order of adenosine&gt;AMP&gt;ADP&gt;ATP, P.sub.2 receptors are activated by ATP, UTP, ADP or UDP and exhibit a potency order of ATP.gtoreq.ADP&gt;AMP&gt;adenosine. As more has become known about the purinergic receptors and the wide range of physiological responses in which they play a role, the P.sub.1 -and P.sub.2 -type classifications were no longer sufficient to accurately portray this complex family of receptors. Therefore, receptor subtype categories have been developed. For example, the P.sub.2 -type purinergic receptors are now classified as P.sub.2Y -, P.sub.2U -, P.sub.2T -, P.sub.2X - and P.sub.2Z -subtypes. A review of the P.sub.2 -type purinergic receptors can be found in Harden, et al., Ann. Rev. Pharmacol. Toxicol. 35:541-579 (1995).
Classification of the P.sub.2 -type purinergic receptors has been difficult because there are no published selective P.sub.2 -receptor antagonists and there are few ATP or ADP receptor-subtype specific agonists. In addition, it has been difficult to compare the relative order of potency of P.sub.2 -purinergic receptor agonists. Hence, this subtype has presented numerous challenges in the identification and characterization of its members.